Pharmacodynamics
Antidepressant, a propylamine derivative. The mechanism of action is associated with the selective blockade of the neuronal reuptake of serotonin in the central nervous system. Fluoxetine is a weak antagonist of choline, adrenergic and histamine receptors. Unlike most antidepressants, fluoxetine does not seem to cause a decrease in the functional activity of postsynaptic β-adrenergic receptors. Improves mood, reduces feelings of fear and tension, eliminates dysphoria. Does not cause sedation. When taken in medium therapeutic doses, it practically does not affect the functions of the cardiovascular and other systems.
Pharmacokinetics
Absorbed from the digestive tract. Poorly metabolized during the "first pass" through the liver. Food intake does not affect the degree of absorption, although it can slow down its rate. Cmax in plasma is reached after 6-8 hours. Css in plasma is reached only after continuous administration for several weeks. Protein binding 94.5%. Easily penetrates the BBB. It is metabolized in the liver by demethylation to form the main active metabolite of norfluoxetine.
T1 / 2 of fluoxetine is 2-3 days, norfluoxetine - 7-9 days. It is excreted by the kidneys 80% and through the intestines - about 15%.
Contraindications
Glaucoma, bladder atony, severe renal dysfunction, benign prostatic hyperplasia, simultaneous administration of MAO inhibitors, convulsive syndrome of various origins, epilepsy, pregnancy, lactation, hypersensitivity to fluoxetine.
Pregnancy and lactation
Contraindicated for use during pregnancy and lactation.
Side effects
From the side of the central nervous system: anxiety, tremor, nervousness, drowsiness, headache, sleep disturbances are possible.
From the digestive system: diarrhea, nausea are possible.
From the side of metabolism: increased sweating, hypoglycemia, hyponatremia are possible (especially in elderly patients and with hypovolemia).
On the part of the reproductive system: decreased libido.
Allergic reactions: possible skin rash, itching.
Others: pain in joints and muscles, difficulty breathing, fever.
Interaction
With simultaneous use with drugs that have a depressing effect on the central nervous system, with ethanol, a significant increase in the inhibitory effect on the central nervous system is possible, as well as an increase in the likelihood of seizures.
With simultaneous use with MAO inhibitors, furazolidone, procarbazine, tryptophan, the development of serotonin syndrome (confusion, hypomania, motor restlessness, agitation, convulsions, dysarthria, hypertensive crisis, chills, tremor, nausea, vomiting, diarrhea) is possible.
With the simultaneous use of fluoxetine inhibits the metabolism of tricyclic and tetracyclic antidepressants, trazodone, carbamazepine, diazepam, metoprolol, terfenadine, phenytoin, which leads to an increase in their concentration in the blood serum, an increase in their therapeutic and side effects.
With simultaneous use, it is possible to inhibit the biotransformation of drugs metabolized with the participation of the CYP2D6 isoenzyme.
When used simultaneously with hypoglycemic agents, their effect may be enhanced.
There are reports of increased effects of warfarin when used simultaneously with fluoxetine.
With simultaneous use with haloperidol, fluphenazine, maprotiline, metoclopramide, perphenazine, peritsiazine, pimozide, risperidone, sulpiride, trifluoperazine, cases of extrapyramidal symptoms and dystonia have been described; with dextromethorphan - a case of hallucinations has been described; with digoxin - a case of an increase in the concentration of digoxin in the blood plasma.
With simultaneous use with lithium salts, it is possible to increase or decrease the concentration of lithium in the blood plasma.
With simultaneous use, it is possible to increase the concentration of imipramine or desipramine in the blood plasma by 2-10 times (it may persist for 3 weeks after discontinuation of fluoxetine).
With simultaneous use with propofol, a case has been described in which spontaneous movements were observed; with phenylpropanolamine - a case was described in which dizziness, weight loss, hyperactivity were observed.
With simultaneous use, it is possible to enhance the effects of flecainide, mexiletine, propafenone, thioridazine, zuclopenthixol.
Dosage and administration
The method of application and dosage regimen of a particular drug depends on its form of release and other factors. The optimal dosage regimen is determined by the doctor. The compliance of the used dosage form of a specific drug with indications for use and dosage regimen should be strictly observed.
The initial dose is 20 mg 1 time / day in the morning; if necessary, the dose can be increased after 3-4 weeks. The frequency of admission is 2-3 times / day.
The maximum daily oral dose for adults is 80 mg.
Special instructions
Use with extreme caution in patients with impaired liver and kidney function, with a history of epileptic seizures, cardiovascular diseases.
In patients with diabetes mellitus, it is possible to change the level of glucose in the blood, which requires correction of the dosage regimen of hypoglycemic drugs. When used in debilitated patients when taking fluoxetine, the likelihood of developing epileptic seizures increases.
With the simultaneous use of fluoxetine and electroconvulsive therapy, prolonged epileptic seizures may develop.
Fluoxetine can be used no earlier than 14 days after the withdrawal of MAO inhibitors. The period after discontinuation of fluoxetine before starting therapy with MAO inhibitors should be at least 5 weeks.
Elderly patients require dosage adjustment.
The safety of fluoxetine in children has not been established.
During the period of treatment, avoid alcohol consumption.
Influence on the ability to drive vehicles and use mechanisms
During the period of treatment, one should refrain from potentially hazardous activities that require increased attention and rapid psychomotor reactions.
